Diagnostic reagents which will reduce technetium from its commercially available valency state of plus seven to a lower valency state so that it may then be bound by a variety of chelating agents are recognized in the art. A large number of such reagents utilize stannous ions as the reducing agent for technetium. It is further recognized that it is necessary to maintain such reagents free of oxygen and oxidants since oxidation of the stannous ions and/or oxidation of the technetium will destroy the reduced technetium chelate.
Previous efforts to protect the reducing capability of stannous tin in such reagents prior to the addition of technetium 99 m pertechnetate include art-recognized means to remove oxygen and oxidants from the reagents and the use of lyophilization. Failure to effectively remove all oxidants, or the presence of residual water in the preparation after lyophilization, however, may result in the slow oxidation of the reducing agent and eventual failure of the reagent. An obvious expeditious solution to the problem would be to increase the concentration of the reducing agent thereby allowing for some loss in reducing power without losing the effectiveness of the reagents. This solution, however, is often undesirable wherein stannous ions are utilized as the reducing agent, since the potential for toxic manifestations increases as the concentration of the reagent administered to the patient is increased.
In addition to the problem of oxidation of the stannous ions in such reagents with resultant loss in stability, there is a second problem with such reagents which is not generally recognized in the art, i.e., alterations in the form of the reagent when the pH is elevated, thought to be due to the tendency of Sn(II) and reduced technetium in aqueous solution to hydrolyze with resultant alteration in the in vivo distribution pattern of the technetium 99 m labeled reagent.
In accordance with the present invention a means has been found to simultaneously stabilize such reagents against both problems enumerated above by the addition to said chelate of a non-toxic, physiologically acceptable, metabolizable substance selected from the group consisting of ascorbic acid, erythorbic acid, pharmaceutically acceptable inorganic salts thereof and mixtures thereof.